Increased Interleukin-10 Expression by the Inhibition of Ca2+-Activated K+ Channel KCa3.1 in CD4+CD25+ Regulatory T Cells in the Recovery Phase in an Inflammatory Bowel Disease Mouse Model

Ohya, Susumu; Matsui, Masanao; Kajikuri, Junko; Endo, Kenji; Kurihara, Hiroaki

doi:10.1124/jpet.120.000395

Cited by 8 publications

(6 citation statements)

References 63 publications

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“…The above phenomenon supports a key role of KCa3.1 in Th0, Th1, and Th2-mediated diseases, including RA, colitis, and several other immune inflammatory disorders ( 80 ). Consistently, pharmacological inhibition of KCa3.1 decreased inflammatory bowel disease mice symptoms via increasing IL-10 production in T reg cells, suggests that KCa3.1 is responsible for the invalidation of anti-inflammatory efficiency of T reg cells in chronic inflammatory disorders ( 81 , 82 ).…”

Section: Regulatory Roles Of Kca31 In Immune Cellsmentioning

confidence: 81%

“…Consequently, decreased secretion of pro-inflammatory factors, such as IL-1β, IL-6, TNF-α, and MCP-1, limits the progression of inflammation ( 102 ). In regulatory T cells, suppression of KCa3.1 channel activity initiates phosphorylation of JNK and c-Jun, activation of JNK/c-Jun signaling, and E4BP4/Blimp1-mediated anti-inflammatory IL-10 cytokine secretion ( 81 , 82 ). The above findings suggest that inhibition of KCa3.1 channel activity modulates immune-inflammatory factors and alleviates inflammation.…”

Section: Correlative Regulation Of Kca31 and Immune-inflammatory Cyto...mentioning

confidence: 99%

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Regulatory role of KCa3.1 in immune cell function and its emerging association with rheumatoid arthritis

et al. 2022

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Rheumatoid arthritis (RA) is a common autoimmune disease characterized by chronic inflammation. Immune dysfunction is an essential mechanism in the pathogenesis of RA and directly linked to synovial inflammation and cartilage/bone destruction. Intermediate conductance Ca2+-activated K+ channel (KCa3.1) is considered a significant regulator of proliferation, differentiation, and migration of immune cells by mediating Ca2+ signal transduction. Earlier studies have demonstrated abnormal activation of KCa3.1 in the peripheral blood and articular synovium of RA patients. Moreover, knockout of KCa3.1 reduced the severity of synovial inflammation and cartilage damage to a significant extent in a mouse collagen antibody-induced arthritis (CAIA) model. Accumulating evidence implicates KCa3.1 as a potential therapeutic target for RA. Here, we provide an overview of the KCa3.1 channel and its pharmacological properties, discuss the significance of KCa3.1 in immune cells and feasibility as a drug target for modulating the immune balance, and highlight its emerging role in pathological progression of RA.

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Section: Regulatory Roles Of Kca31 In Immune Cellsmentioning

confidence: 81%

Section: Correlative Regulation Of Kca31 and Immune-inflammatory Cyto...mentioning

confidence: 99%

Regulatory role of KCa3.1 in immune cell function and its emerging association with rheumatoid arthritis

et al. 2022

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“…In this prolonged rapid atrial pacing model, macrophage pro-inflammatory polarization and inflammatory cytokine secretion are alleviated by KCa3.1 inhibition, which is likely through the p38 MAPK/AP-1/ NF-kB signaling pathway [30]. Again using TRAM34, Ohya et al reported that pharmacological inhibition of KCa3.1 increases interleukin-10 production in peripheral T reg cells and improves abdominal symptoms in a mouse model of inflammatory bowel diseases [31].…”

Section: Pathophysiological Roles Of Kca31mentioning

confidence: 91%

KCa3.1 in diabetic kidney disease

Huang

Chen²,

Pollock³

2021

Current Opinion in Nephrology &Amp; Hypertension

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Purpose of reviewDiabetic kidney disease (DKD) is a significant health concern. Innovative strategies to prevent or limit the progression of DKD are urgently needed due to the limitation of existing treatments. KCa3.1, a potassium channel, is involved in a range of biological processes from cell survival to cell death. This review summarizes the current knowledge on the pathophysiological functions of the KCa3.1 channel, specifically its involvement in maintaining mitochondrial function. More specifically, the therapeutic potential of targeting KCa3.1 in DKD is systematically discussed in the review. Recent findingsMitochondrial dysfunction contributes to the development and progression of DKD. Accumulating evidence indicates that KCa3.1 dysregulation plays a crucial role in mitochondrial dysfunction, in addition to driving cellular activation, proliferation and inflammation. Recent studies demonstrate that KCa3.1 deficiency improves diabetes-induced mitochondrial dysfunction in DKD, which is attributed to modulation of mitochondrial quality control through mitigating the altered mitochondrial dynamics and restoring abnormal BNIP3-mediated mitophagy.

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“…178) A treatment with an IK channel blocker was found to be beneficial in the recovery phase. 179) Although the pharmacological blockade of KCa3.1 may reduce the risk of developing IBD, the possibility of a double-edged sword has also been suggested. 180) IK channels are engaged in the pathogenesis of delayed-type hypersensitivity (DTH) in the auricular lymph node CD44 + T lymphocytes of oxazolone-induced DTH model mice.…”

Section: -1 Bk Channel-related Diseases and Modulator Pharmacologymentioning

confidence: 99%

Reciprocal Relationship between Ca2+ Signaling and Ca2+-Gated Ion Channels as a Potential Target for Drug Discovery

Imaizumi

2022

Biological & Pharmaceutical Bulletin

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Cellular Ca 2 signaling functions as one of the most common second messengers of various signal transduction pathways in cells and mediates a number of physiological roles in a cell-type dependent manner. Ca 2 signaling also regulates more general and fundamental cellular activities, including cell proliferation and apoptosis. Among ion channels, Ca 2 -permeable channels in the plasma membrane as well as endo-and sarcoplasmic reticulum membranes play important roles in Ca 2 signaling by directly contributing to the influx of Ca 2 from extracellular spaces or its release from storage sites, respectively. Furthermore, Ca 2 -gated ion channels in the plasma membrane often crosstalk reciprocally with Ca 2 signals and are central to the regulation of cellular functions. This review focuses on the physiological and pharmacological impact of i) Ca 2 -gated ion channels as an apparatus for the conversion of cellular Ca 2 signals to intercellularly propagative electrical signals and ii) the opposite feedback regulation of Ca 2 signaling by Ca 2 -gated ion channel activities in excitable and non-excitable cells.Key words Ca 2+ signaling; Ca 2+ microdomain; ion channel; Ca 2+ permeable channel; Ca 2+ -activated K + channel; Ca 2+ -activated Cl − channel 2-1. Ca 2+ -Gated Ion Channels The established classification and nomenclature of ion channels need to be referred to those presented by The International Union of Basic and Clinical Pharmacology (IUPHAR) (https://www.guideto pharmacology.org/). 3) One of the practical classifications of ion channels may be that based on gating mechanisms. Table 1 proposes a classification of ion channels on the PM based on their gating mechanisms. RyRs and IP 3 Rs are channels in ER/SR membranes, but are also listed here because of their close involvement in the issues discussed in this review.In this classification, "Ca 2+ -gated ion channels" refer to channels for which an increase in [Ca 2+ ] i is an essential factor for their activation. The Ca 2+ -gated K + channel family consists of three subfamilies classified by channel conduc-

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Increased Interleukin-10 Expression by the Inhibition of Ca²⁺-Activated K⁺ Channel K_Ca3.1 in CD4⁺CD25⁺ Regulatory T Cells in the Recovery Phase in an Inflammatory Bowel Disease Mouse Model

Cited by 8 publications

References 63 publications

Regulatory role of KCa3.1 in immune cell function and its emerging association with rheumatoid arthritis

Regulatory role of KCa3.1 in immune cell function and its emerging association with rheumatoid arthritis

KCa3.1 in diabetic kidney disease

Reciprocal Relationship between Ca<sup>2+</sup> Signaling and Ca<sup>2+</sup>-Gated Ion Channels as a Potential Target for Drug Discovery

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